The primary objective of this project is the investigation of immunoregulatory phenomena in vivo and in vitro and is generally based on the premise that the immune system is not tolerant of self components that are expressed only transiently by activated cells. We hypothesize that some activation markers present on certain cells function as self-superantigens for T cells. The results of our experiments show that T(H)2 cells acquire upon activation, the ability to stimulate T cells polyclonally, particularly CD8+ cells. The activation requires cell-cell interactions and is independent of released lymphokines. We hypothesize that the physiological purpose of this anti-self response is to couple the activation' events characteristic of all immune responses with immunoregulatory circuits based on help and suppression: the engagement of additional CD4+ cells produces amplificatory circuits while the activation of CD8+ cells brings about suppression and/or killing of activated cells. Neither one of these two processes is antigen-specific, although they are both initiated by antigen-specific events, i.e., the activation of the "inducer" T(H)2 clones In vitro or their counterparts in vivo. I propose a sat of studies aimed at investigating different aspects of immunoregulatory T-T interactions In vitro and In vivo, their specificity and functional significance. In addition, I propose to investigate the functional role of T cell Ia in antigen presentation and tolerance induction and to explore the immunoregulatory effects of monoclonal antibodies bound to FcR present on T cells.